Photo Credit: Stanislau Kharytanovich

The earlier introduction of inclisiran significantly reduced low-density lipoprotein concentrations without affecting statin compliance in patients with atherosclerotic cardiovascular disease in the phase 3b VICTORIAN-INITIATE trial.

The earlier introduction of inclisiran significantly reduced low-density lipoprotein (LDL) concentrations without affecting statin compliance in patients with atherosclerotic cardiovascular disease (ASCVD) in the phase 3b VICTORIAN-INITIATE trial. More than 80% of patients achieved the LDL treatment goal of less than or equal to 70 mg/dL.

Inclisiran is a first-in-class, long-acting, synthetic small-interfering RNA molecule directed against PCSK9 that has been shown to cause a marked reduction in LDL-C levels. Twice-yearly injections can lower LDL concentration by an additional 50%. In the current prospective, multicenter, randomized, open-label phase 3b trial VICTORION-INITIATE (NCT04929249), Michael Koren, MD, and colleagues assessed whether an “inclisiran first” implementation strategy (ie, adding inclisiran immediately when patients fail to reach LDL-C <70 mg/dL despite receiving maximally tolerated statins) can help to control LDL concentrations in patients with a history of ASCVD.

All 450 participants received maximum-tolerated statin therapy or had documented statin intolerance without achieving LDL-C less than or equal to 70 mg/dL. The study team randomly assigned participants to the “inclisiran first” strategy or usual care, with lipid-lowering therapy left to the treating physician’s discretion. The study’s coprimary endpoints were the percentage change in LDL-C from baseline to day 330 and the discontinuation of statin therapy, defined as no statin use for at least 30 days before the end-of-study visit.

At day 330, the mean percentage change in LDL-C from baseline was -60.0% (97.5% CI -64.7 to -55.2) with the “inclisiran first” intervention and only -7.0% (97.5% CI -12.0 to -1.9) with usual care; a statistically significant difference (LS mean difference -53.0%; 97.5% CI -60.0 to -46.0; P<0.001). Statin discontinuation rates with “inclisiran first” (6.0%) were noninferior versus usual care (16.7%). In the “inclisiran first” group, 81.8% of participants met their LDL treatment goal compared with 22.2% in the usual care group (P<0.001).

The safety profile of both approaches was similar, except for injection-site reactions that were more frequent in the “inclisiran first” strategy (10.3% versus 0 in the usual care group).

Medical writing support was provided by Dr. Susanne Kammerer.
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